Injured sensory neurons-derived Galectin-3 contributes to neuropathic pain via programming microglia in the spinal dorsal horn
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE242769 | GEO | 2025/09/01
REPOSITORIES: GEO
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Project description:Objective: Chronic pain is a major problem in patients with spinal cord injury (SCI). According to different studies, approximately 70% of patients with SCI experience persistent pain. Although previous gene expression profiling studies have been conducted in animal models, gene expression profiling study in human whole blood has not been reported yet. The objective of this study was to define the gene expression profile of neuropathic pain in spinal cord injured patients. Materials and Methods: We performed gene expression analysis including 20.000 genes using Affymetrix GeneChip® Primeview™ Human Gene Expression Arrays. For confirmation of expression levels of selected genes, we performed real time polymerase chain reaction. We gathered samples from periferic blood mononuclear cells. Data of twelve patients with intractable neuropathic pain was compared with thirteen patients who don’t have pain. All patients have complete injuries with a level of injury above T5. Results: A total of 16 differentially expressed genes including 9 up-regulated and 7 down-regulated were obtained with a cut-off degree at 4 fold change. EIF1AY, RPS4Y1, DDX3Y, RPL31, ETS1, KLF3, JUN, CYorf15B, and ERAP2 were in up-regulated and HLA-C, XIST, C4BPA, FAM118A, ZNF506, OVOS2, and C1D were in down-regulated group. KEGG pathway database showed that 14.6% of genes were enriched in the nodes of immune system. Real time polymerase chain reaction analyses did not increase to statistically significant levels for confirmation of gene expression analyze results. Conclusions: Considering these data, findings of this first gene expression study in humans with SCI might provide valuable information for future targets for understanding neuropathic pain pathogenesis. The results of gene expression analyses were not confirmed by real time polymerase chain reaction. Studies with larger sample size are needed for confirmation. This is a cross-sectional study with a control group. Patients were divided into two groups according to intractable neuropathic pain existence.There were 12 patients in group A (Patients with pain) and 13 patients in control group.
2015-06-16 | E-GEOD-69901 | biostudies-arrayexpress
Project description:Neuropathic pain (NP) is a complex and common chronic pain that affects millions of people worldwide. Previous studies showed that prior exercise protects against NP caused by nerve injury, but the mechanisms remain elusive. Therefore, this study aimed to identify the differentially expressed proteins (DEPs) involved in the process of protecting against NP by prior exercise and explore the underlying mechanisms through bioinformatic analysis.
2025-05-07 | PXD054342 | Pride
Project description:Recent studies reveal that microglia modulate synaptic transmission by direct synaptic pruning. Microglia reactivation is a crucial mechanism of central sensitization in neuropathic pain, yet the exact changes of microglia during the development of neuropathic pain and its interaction with the spinal inhibitory circuits remains unclear. In this work, single-cell sequencing delineates temporal changes in spinal microglia and identifies a specific type of microglia as the subpopulation mediating synaptic pruning. We found that peripheral nerve injury induced the transition of spinal microglia from a pro-inflammatory to a “pruning” state, resulting in pain hypersensitivity by spinal disinhibition.
2024-10-24 | GSE246288 | GEO
Project description:In settings of heightened pain sensitivity, such as following peripheral nerve injury (PNI) or opioid-induced hyperalgesia (OIH), microglia take on an activated phenotype. Functional studies have suggested that microglia activated by PNI or chronic opioids then engage common mechanisms to facilitate pain. Here we conducted RNA sequencing of acutely isolated spinal cord microglia to comprehensively interrogate commonality between PNI and OIH. By combining our results with meta-analysis of published datasets, we identify transcriptional signatures of microglial reactivity that differ between PNI models over time, opioid exposure, or CNS pathology, despite similar histological outcomes. Collectively, these results reveal a discrepancy between histological markers of activation and transcriptional response, and provide a resource of pain-associated microglial transcriptomes that caution against a universal signature of microglia activation.
2022-01-03 | GSE117320 | GEO
Project description:In settings of heightened pain sensitivity, such as following peripheral nerve injury (PNI) or opioid-induced hyperalgesia (OIH), microglia take on an activated phenotype. Functional studies have suggested that microglia activated by PNI or chronic opioids then engage common mechanisms to facilitate pain. Here we conducted RNA sequencing of acutely isolated spinal cord microglia to comprehensively interrogate commonality between PNI and OIH. By combining our results with meta-analysis of published datasets, we identify transcriptional signatures of microglial reactivity that differ between PNI models over time, opioid exposure, or CNS pathology, despite similar histological outcomes. Collectively, these results reveal a discrepancy between histological markers of activation and transcriptional response, and provide a resource of pain-associated microglial transcriptomes that caution against a universal signature of microglia activation.
2022-01-03 | GSE117319 | GEO
Project description:Neuroinflammation is a major component in the transition to and perpetuation of neuropathic pain states. Spinal neuroinflammation involves activation of TLR4, localized to enlarged, cholesterol-enriched lipid rafts, designated here as inflammarafts. Conditional deletion of cholesterol transporters ABCA1 and ABCG1 in microglia, leading to inflammaraft formation, induced tactile allodynia in naïve mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reversed neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN) in wild-type mice, but AIBP failed to reverse allodynia in mice with ABCA1/ABCG1-deficient microglia, suggesting a cholesterol-dependent mechanism. An AIBP mutant lacking the TLR4-binding domain did not bind microglia nor reversed CIPN allodynia. The long-lasting therapeutic effect of a single AIBP dose in CIPN was associated with anti-inflammatory and cholesterol metabolism reprogramming and reduced accumulation of lipid droplets in microglia. These results suggest a cholesterol-driven mechanism of regulation of neuropathic pain by controlling TLR4 inflammarafts and gene expression program in microglia and blocking the perpetuation of neuroinflammation.
2021-04-16 | GSE154816 | GEO
Project description:Microglia have been implicated in the pathophysiology of neuropathic pain. Here, we sought to investigate whether cerebrospinal fluid (CSF) might be used as a proxy-measure of microglial activation in human participants. For this, we preformed fluorescent-activated cell sorting (FACS) of CSF immune cell populations derived from individuals who experienced pain with neuropathic features. We sorted CD4+, CD8+ T cells and monocytes and analyzed their transcriptome using RNA sequencing. We also performed Cellular Indexing of Transcriptomes and Epitopes (CITE)-seq to characterize the expression of all CSF immune cells in a patient with postherpetic neuralgia and in a patient with neuropathic pain after failed back surgery. Immune cell numbers and phenotypes were not obviously different between individuals regardless of the etiology of their pain. This was true when examining our own dataset, as well as when comparing it to previously published single-cell RNA sequencing data of human CSF. In all instances, CSF monocytes showed expression of myeloid cell markers commonly associated with microglia (P2RY12, TMEM119 and OLFML3), which will make it difficult to ascertain the origin of CSF proteins: do they derive directly from circulating CSF monocytes or could some originate in spinal cord microglia in the parenchyma? We conclude that it will not be straightforward to use CSF as a biomarker for microglial function in humans.
2023-10-03 | GSE244499 | GEO
Project description:Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein synthesis; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found mTOR activation in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. Combining transcriptomic profiling, electrophysiological recording and pharmacologic manipulations, we demonstrated that activated mTOR promoted neuropeptide Y (NPY) induction in mechanoreceptors and that NPY acted on Y2 receptors (Y2R) but not Y1R to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented its function. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.
2022-09-01 | GSE184014 | GEO
Project description:Neuropathic pain is a prevalent and debilitating chronic disease that is characterized by activation in glial cells in various pain-related regions within the central nervous system. Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis of microglia to identify whether there is a common neuropathic microglial signature and characterize the sex differences in microglia in pain-related regions in nerve injury and chemotherapy-induced peripheral neuropathy mouse models. Whilst mechanical allodynia and behavioral changes were observed in all models, transcriptomic analysis of microglia revealed no common transcriptional changes in spinal and supraspinal regions and in different neuropathic models. However, there was a substantial change in microglial gene expression within the ipsilateral lumbar spinal cord 7-days after chronic constriction injury (CCI) of the sciatic nerve. Both sexes upregulated genes associated with inflammation, phagosome, and lysosome activation, though males revealed a prominent global transcriptional shift not observed in female mice. This study demonstrates a lack of a common neuropathic microglial signature and indicates distinct sex differences in spinal microglia, suggesting they contribute to the sex-specific pain processing following nerve injury.
2021-07-27 | GSE180627 | GEO
Project description:Intractable neuropathic pain is recognized as a common symptom of neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism of NMOSD pain remains to be elucidated. Here, we established NMOSD pain model by injecting anti-AQP4 recombinant autoantibodies (AQP4-Ab) generated from NMOSD patient’s plasmablasts into rat spinal cords and confirmed the development of mechanical allodynia. AQP4-Ab mediated extracellular ATP release from astrocytes and pharmacological inhibition of ATP receptor reversed mechanical allodynia in NMOSD pain model. Furthermore, transcriptome analysis revealed microglia activation and IL-1β elevation in NMOSD spinal cord. Inhibition of microglia activation and neutralization of IL-1β also attenuated neuropathic pain in NMOSD rat model. In addition, the human CSF ATP concentration was significantly higher in the acute and remission phase of NMOSD than in multiple sclerosis and other neurological disorder patients. These findings indicate ATP, microglial activation and IL-1β secretion orchestrates the pathogenesis of NMOSD neuropathic pain.
2021-08-24 | GSE150598 | GEO